Biocompatibility and in vivo morphine diffusion into a placebo morphine-triggered naltrexone delivery device in rabbits

Two key factors in developing a clinically useful triggered naltrexone delivery system are device biocompatibility and ability of morphine to diffuse from the blood into the device in concentrations useful to trigger delivery. Two types of devices were implanted subcutaneously into rabbits and their biocompatibility investigated. One device consisted of the outer semipermeable regenerated cellulose acetate tubing, closed at both ends with double knots and filled with poly(N-vinyl pyrrolidone) as osmotic filler. The other device was a placebo device that contained within the regenerated cellulose acetate tubing, also closed at both ends with double knots, all device components except naltrexone. Both devices were biocompatible. When the regenerated cellulose acetate device filled with osmotic filler was implanted in rabbits which were subsequently dosed at day 7 and day 14 post-implant with 150 mg kg−1 morphine sulphate, the concentration of morphine in the device was only about 10-fold less than that measured in rabbit blood. Thus, enough morphine diffuses into the device to make triggering in a real-life situation feasible.